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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 325 records · Page 18Linked to original sources
PubMed1997

Frequent hepatic involvement in adult T cell leukemia: comparison with non-Hodgkin's lymphoma.

We examined 111 patients with acute type- or lymphoma type-adult T-cell leukemia (ATL) and compared them with 106 patients with non-Hodgkin's lymphoma (NHL). In addition to skin involvement and hypercalcemia which are already known to be frequent in ATL, ATL patients showed an higher incidence of hepatic involvement. There was more frequent palpable hepatomegaly, higher total bilirubin, GOT, GPT, lactate dehydrogenase (LDH), and alkaline phosphatase values in ATL than in NHL patients (p < 0.0001). Among 36 autopsied liver samples, invasion of ATL cells was confirmed in 22 cases. ATL patients with impaired hepatic function showed shorter survival times than patients without hepatic dysfunction. Moreover, ATL patients showed a worse performance status (PS), a higher incidence of lytic bone lesions, lower total protein (TP) and serum albumin levels than NHL patients. This invasive characters of ATL cells and consequent impaired general condition seemed to be factors affecting the poor prognosis recorded in ATL.

Adult↗
PubMed1997

[Juvenile cerebral infarction with familial hyperlipoproteinemia (a)--case report].

A 34-year-old male with a history of angina pectoris suddenly developed weakness in the right upper and lower limbs, and consulted our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested cerebral infarction. Cerebral angiography revealed stenosis at the M1 portion of the left middle cerebral artery. Hypertension, diabetes, tobacco or hyperlipidemia were not considered as risk factors for cerebral infarction. The lipoprotein (a) [Lp(a)] level was high. In the present case, medication with a nicotinic acid agent, niceritrol, for hyperlipoproteinemia and low density lipoprotein (LDL) apheresis were performed. Concerning family history, the patient's mother and younger sister had hyperlipoproteinemia. Recent studies have reported that increased Lp(a) levels are an independent risk factor even in cerebral infarction and coronary artery disease. Measurement of Lp(a) levels and treatment for increased Lp (a) levels may be important.

Adult↗
PubMed1997

[Clinical efficacy of GG032X tablets, a new dosage form of ondansetron (fast dispersing tablet), on cisplatin-induced nausea and emesis].

The inhibitory effects of GG032X tablets, a new dosage form (fast dispersing tablet) of ondansetron, 5-HT2 receptor antagonist, on nausea and emesis induced by cisplatin (CDDP), were investigated along with safety and usefulness. Subjects were chemotherapy patients starting CDDP administration for the first time, who were receiving a high single dose of CDDP (50 mg/m2 or more and intravenous drip infusion of less than 4 hours), or lower multiple doses of CDDP (a single dose of 10 mg/m2 or more, administered intravenously for 3-5 consecutive days). GG032X tablets were administered orally 1-2 hours before CDDP administration. In lower multiple doses of CDDP, GG032X tablets and CDDP were administered, as much as possible, at the same respective time when they were administered on the first day. Efficacy of GG032X tablets was evaluated in terms of inhibitory effect on nausea and emesis 24 hours after administration of a high single dose of CDDP, and of the inhibitory effect on nausea and emesis during the study period (3-5 days) in lower multiple doses of CDDP. Efficacy, safety and usefulness were evaluated in accordance with the evaluation criteria used in the clinical study of already-approved ondanstron tablets. In a high single dose of CDDP, the cases judged "effective" or better in the investigation of the inhibitory effect of the drug on nausea and emesis, accounted for 52.9% (63/119 cases). As for the overall safety rating, the cases judged as "safe" accounted for 87.0% (107/123 cases), and as a "minor safety problem" accounted for 13.0% (16/123 cases). As for the usefulness rating, the cases judged "useful" or better accounted for 52.1% (62/119 cases). Major adverse effects included headache, fever, atrial fibrillation and increases in total bilirubin, GOT and GPT values. None of these was serious, and the patients recovered without any treatment or by nosotropic therapy. Meanwhile, in lower multiple doses of CDDP, the inhibitory effect judged "effective" or better accounted for 70.6% (12/17 cases). As for the overall safety rating, all cases were judged "safe". In terms of usefulness, those cases judged "useful" or better accounted for 70.6% (12/17 cases). No adverse effect was observed. Study results of these two groups were almost the same as those for already-approved ondansetron tablets. According to the results of questionnaires for the patients who participated in the study and took GG032X tablets, the drug was found to be easy to take and had favorable results. Based on the above results, GG032X tablets were evaluated as having the same inhibitory effect as the already-approved ondansetron tablets against CDDP-induced nausea and emesis, and were considered safe and clinically useful.

Administration, Oral↗
PubMed1997

[TUT-7 phase I clinical study. TUT-7 Study Group].

A phase I study with TUT-7, a new anthracycline antitumor antibiotic, was conducted in 35 malignant tumor patients at 11 institutions nationwide. The study was initiated with a single dose at 100 mg/body which was equivalent to 2n, then the dose as escalated up to 700 mg/body in accordance with the modified Fibonacci's scheme. The dose limiting factor (DLF) was considered to be leukopenia, and maximum tolerated dose (MTD) was 700 mg/ body. The consecutive days dosing study subsequently conducted started with 25 mg/body/day, and the dose level was escalated up to 150 mg /body/day. TUT-7 was orally administered for seven (7) to fourteen (14) consecutive days in principle. It was considered that DLF was leukopenia and MTD was 100 mg/body/day for consecutive days dosing. The study indicated that serum drug concentrations reached their plateaus on the 5th day after initiation of TUT-7 treatment and the accumulation of this compound was low. With these findings, a regimen with a dose of 100 mg/body/day orally administered for 14 consecutive days was recommended for early phase II studies.

Administration, Oral↗
PubMed1997

[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies].

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).

Adult↗
PubMed1997

[Menogaril (TUT-7) late phase II study for malignant lymphoma, adult T-cell leukemia and lymphoma (ATLL)].

A late Phase II multicenter study with menogaril was conducted nationwide in patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD)], and ATLL, menogaril was orally administered at 100 mg daily after breakfast, for seven consecutive days with two- or three-week drug withdrawal, then menogaril administration was repeated. For malignant lymphoma, in 81 patients with NHL and 5 patients with HD registered, 70 and 5 patients were evaluable for efficacy, respectively. The efficacy rates were 32.9% (6 CRs + 17 PRs/70) for NHL and 20.0% (1 PR/5) for HD, respectively; that for the NHL patients with prior anthracycline antibiotic chemotherapy was 30.5% (5 CRs and 13 PRs/59). For ATLL, among the 16 patients registered, 15 were evaluable for efficacy, and the efficacy rate was 40.0% (2 CRs and 4 PRs/15). Adverse drug reactions frequently observed in the patients with malignant lymphoma and ATLL included bone-marrow suppression and gastrointestinal symptoms such as anorexia, and nausea/vomiting. With these results, menogaril was considered to be effective for the treatment of non-Hodgkin's lymphoma and ATLL.

Administration, Oral↗
PubMed1997

Experience with UFT in Japan.

The selective antineoplastic effect of tegafur and uracil (UFT) is attributed to its preferential enhancement of fluorouracil concentration in tumor tissues compared with that in normal tissues. The result of this effect is evident in the clinical benefit and lower toxicity associated with UFT compared with other fluorinated pyrimidines. Beginning with preclinical studies in the 1980s, significant therapeutic advantages of UFT have been reported in numerous trials conducted in Japan, including phase I dose-finding studies, phase II multicenter studies, comparative studies, and combination-chemotherapy studies. In phase II studies conducted at 211 institutions, for example, it was shown that the response rate was over 30% in patients with head/neck, bladder, or breast cancer, and the survival rate was superior to that previously reported in Japanese studies. Two comparative studies suggested that UFT was more effective than single-agent tegafur, and a number of combination-chemotherapy studies have shown that it has an advantage in terms of toxicity, response, and/or survival. UFT is also useful for postoperative adjuvant therapy, as well as therapy for advanced disease in a variety of neoplasms. UFT holds considerable promise and future trials should continue the evaluation and refinement of its role in the treatment of cancer.

Chemotherapy, Adjuvant↗
PubMed1997

[A case of systemic lupus erythematosus associated with minimal change nephrotic syndrome].

A case of systemic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) in a 25-year-old female is described. The patient suddenly manifested butterfly rash and proteinuria was first pointed out on March, 1994. On admission, her skin biopsy indicated SLE. Subsequently, she developed nephrotic syndrome. Urinalysis showed heavy proteinuria (4.1 g/day), with no other abnormalities in the urinary sediment. Immunological examination revealed positive antinuclear antibody at a titer of 1:80 with a speckled pattern. Anti-ssDNA and anti-SS-A antibodies were positive, but other antibodies were negative. Serum complement (CH50) was within the normal range (30.5 U/ml). The renal biopsy showed no apparent cellular proliferation or increase of extracellular matrices in glomeruli by light microscopy. Slight deposition of IgG, IgM, C3 and C1q was focally seen in the mesangium and capillary wall by immunofluorescence. Electron microscopic examination revealed small and scattered dense deposits in the mesangium, subepithelium and subendothelium, associated with diffuse fusion of the foot processes of epithelial cells along the glomerular basement membrane. According to the WHO classification, the histological features were compatible with those of lupus nephritis (LN), class Ib. The patient was treated with PREDNISOLONE, Mizorbine and Dilazep, resulting in the disappearance of proteinuria and a normal serum level of total protein. The association of LN and MCNS is very rare. We also investigated the relationship between the intensity of proteinuria and histological types of 53 cases with LN examined in our laboratory. The cases with heavy proteinuria were mostly classified as WHO-Class IV and Class V. We report here a case of LN associated with MCNS and also review the literatures.

Adult↗
PubMed1997

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗
PubMed1996

Age-associated changes in the template-reading fidelity of DNA polymerase alpha from regenerating rat liver.

DNA polymerases (deoxynucleosidetriphosphate: DNA deoxynucleotidyltransferase EC 2.7.7.7.) were extracted from regenerating livers from young and aged rats. DNA polymerase alpha was separated and partially purified by DEAE-cellulose column chromatography, polyethyleneglycol precipitation, and phosphocellulose column chromatography, and fidelity levels were then monitored with the synthetic template-primer poly (dG-dC). The fidelity level of the DNA polymerase from regenerating liver a 4-month-old rat was very high, while that of the DNA polymerase from a 24-month-old rat was significantly decreased. To confirm this result, DNA was synthesized on poly (dG-dC) in a reaction mixture containing [32P]dTTP, and the synthetic polynucleotide was purified and digested with HhaI restriction endonuclease. After hydrolysis, the oligonucleotides were developed by two dimensional thin layer chromatography on PEI cellulose plates. Spots containing [32P]dTMP were observed when DNA polymerase from a 24 month-old rat was used, but none was found in polynucleotides synthesized using DNA polymerase from a 4 month-old rat. Nearest neighbor analysis suggested that dG-dT and dC-dT pairs were constructed by mis-incorporation due to DNA polymerase alpha.

Aging↗
PubMed1996

Age-related changes in proliferating cell nuclear antigen levels.

To clarify the effect of aging on rat liver regeneration, we compared proliferating cell nuclear antigen (PCNA) levels in control and regenerating livers from young and aged rats 48 h after partial hepatectomy. The nucleoplasm and cytoplasm from regenerating livers of 2-month and 24 month-old rats were fractionated by phosphocellulose column chromatography, aliquots of fractions were transferred to nitrocellulose filters and the amounts of PCNA in each fraction were measured by an immunostaining method. Two forms of PCNA, L type (eluted at low concentrations of KC1) and H type (eluted at high KC1 concentrations) were observed in the nucleoplasm from both control and regenerating young rat liver. On the other hand, the cytoplasm contained P type (eluted in the pass-through fraction), L type and H type PCNA. In control liver from aged rats, three types of PCNA in the cytoplasm and two types in the nucleoplasm were present at decreased levels. In regenerating liver from young rats, the increases in L type in the cytoplasm and H type in the nucleoplasm were remarkable. However, none of the three PCNA types increased significantly during liver regeneration in aged rats. Treatment with DNase resulted in the disappearance of the H type with a concomitant increase in the P and L types. These results suggest that the H type is a complex form consisting of the P and L types of PCNA and DNA. These results suggest that the increase in the L type in the cytoplasm reflects newly synthesized PCNA production for cellular proliferation and that the increase in the H type in the nucleoplasm is a reflection of binding to DNA and the fundamental role of PCNA itself in liver regeneration in young rats. On the other hand, there was little increase in any of the three types in regenerating liver from 24-month-old rats. Thus, PCNA content may be closely related to the decrease in the rate of cellular proliferation in aged animals.

Aging↗
PubMed1996

Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9.

We report a novel human gene whose product specifically associates with the negative regulatory domain of the Wilms' tumor gene product (WT1) in a yeast two-hybrid screen and with WT1 in immunoprecipitation and glutathione S-transferase (GST) capture assays. The gene encodes a 17-kDa protein that has 56% amino acid sequence identity with yeast ubiquitin-conjugating enzyme (yUBC) 9, a protein required for cell cycle progression in yeast, and significant identity with other subfamilies of ubiquitin-conjugating enzymes. The human gene fully complements yeast that have a temperature-sensitive yUBC9 gene mutation to fully restore normal growth, indicating that we have cloned a functionally conserved human (h) homolog of yUBC9. Transcripts of hUBC9 of 4.4 kilobases (kb), 2.8 kb, and 1.3 kb were found in all human tissues tested. A single copy of the hUBC9 gene was found and localized to human chromosome 16p13.3. We conclude that hUBC9 retains striking structural and functional conservation with yUBC9 and suggest a possible link of the ubiquitin/proteosome proteolytic pathway and the WT1 transcriptional repressor system.

Amino Acid Sequence↗
PubMed1996

Detection of aneuploidy in interphase nuclei from non-small cell lung carcinomas by fluorescence in situ hybridization using chromosome-specific repetitive DNA probes.

Interphase fluorescence in situ hybridization (FISH) is particularly useful for detecting chromosome changes in tumors exhibiting a low mitotic index, as is the case in many human non-small cell lung carcinomas (NSCLCs). A panel of centromeric DNA probes specific for the autosomes 6, 7, 8, 9, 12, 17, and 18 was used to analyze 17 primary NSCLCs. Evidence for aneuploidy was obtained in all specimens. Gain of part or all of chromosome 7 was especially prominent, occurring in a large population of cells in each of 14 tumors (82%). Extra centromeric copies of chromosomes 6, 12, and 17 were also common, being observed in 9 to 11 cases each. Gain of chromosome 9 was infrequent (three tumors). In two cases, most of the nuclei had only a single chromosome 9 fluorescent signal. Karyotypic findings were available for six cases and were generally consistent with the FISH data. Both methods revealed considerable heterogeneity within individual tumors. NSCLC specimens from 26 males were assayed with a Y-specific centromeric sequence; loss of the Y was observed in 13 cases (50%). These investigations demonstrate the feasibility of interphase FISH for the successful analysis of numerical chromosome changes in NSCLCs.

Aneuploidy↗